Peering deeply – and quite literally – into the intact brain: A video fly-through

CLARITY, pioneered by Stanford psychiatrist/bioengineer Karl Deisseroth, MD, PhD, renders intact tissue samples transparent. Above is a video clip showing off the new method’s capabilities. First you’ll witness a “fly-through” of a complete mouse brain using fluorescent imaging. The immediately following clip – it’s spectacular! – provides a three-dimensional view of a mouse hippocampus (the brain’s brain’s memory hub), with projecting neurons depicted in green, connecting interneurons in red, and layers of support cells, or glia, in blue.

Note that in both cases, there was no need to slice the tissue into ultra-thin sections, analyze them chemically and/or optically and then laboriously “sew” them back together via computer algorithms in order to reconstruct a 3-D virtual image of the biological sample. All that was required, after performing the necessary hocus-pocus, was to ”send in the stain” (i.e., use histochemical means to paint different cell types different colors) and move the sample or camera lens or shift the latter’s focal length. Nice trick. With big implications for biomedical research.

Purkinje neurons play an essential role in motor function. Here the Purkinje neurons reach their arbor-like dendrites into the molecular layer of the developing cerebellum of a mouse. The mostly green cells at the bottom left are cerebellar granule cells, which relay information from the nervous system to the Purkinje neurons.
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Purkinje neurons play an essential role in motor function. Here the Purkinje neurons reach their arbor-like dendrites into the molecular layer of the developing cerebellum of a mouse. The mostly green cells at the bottom left are cerebellar granule cells, which relay information from the nervous system to the Purkinje neurons.

Source: download.cell.com

Keloid Scars Scars are formed by the collagen produced by fibroblasts in the area of the injury. Initially scars may have a raised or bumpy appearance, but over time tend to diminish in size and flatten. Sometimes, however, fibroblasts do not cease to produce collagen at the proper time, and the resultant scar swells with the fibrous protein to unusual proportions. If this growth remains restricted to the original location of the wound then it is referred to as a hypertrophic scar, but if it extends past the boundaries of the injured area, then the overgrown scar is called a keloid.
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Keloid Scars

Scars are formed by the collagen produced by fibroblasts in the area of the injury. Initially scars may have a raised or bumpy appearance, but over time tend to diminish in size and flatten. Sometimes, however, fibroblasts do not cease to produce collagen at the proper time, and the resultant scar swells with the fibrous protein to unusual proportions. If this growth remains restricted to the original location of the wound then it is referred to as a hypertrophic scar, but if it extends past the boundaries of the injured area, then the overgrown scar is called a keloid.

Source: microscopyu.com

The Human Brain in cross section (near the midline) The following structures can be located here: Cerebellum, 4th ventricle, Superior colliculus, Inferior colliculus, Periaqueductal gray, Pons, Dorsal funiculus, MLF, Medial lemniscus, Red nucleus, Mammillary body, Pineal body, Posterior commissure, Anterior commissure, Thalamus, and Fornix.
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The Human Brain in cross section (near the midline)

The following structures can be located here:

Cerebellum, 4th ventricle, Superior colliculus, Inferior colliculus, Periaqueductal gray, Pons, Dorsal funiculus, MLF, Medial lemniscus, Red nucleus, Mammillary body, Pineal body, Posterior commissure, Anterior commissure, Thalamus, and Fornix.

Source: medicine.creighton.edu

In the hippocampus, neural stem cells (green) sit in a layer below their progeny, the granule neurons (red). When activated by extrinsic stimuli, they enter mitosis and generate neuron progenitor cells, which eventually mature into neurons and migrate into the layer above. The number of neural stem cells in the hippocampus decreases over time, possibly contributing to the cognitive impairment associated with aging. One hypothesis is that, after a rapid series of divisions, these neural stem cells disappear via their conversion into astrocytes. Image: Section of a mouse hippocampus imaged with Zeiss LSM 50 confocal microscope with a 40X C-Apochromat water-immersion objective lens (N.A. value 1.2, working distance 220 microns) at 62x magnification. Brain slices were fixed in 4% paraformaldehyde, immunolabeled, and then cleared in FocusClear (CelExplorer, Taiwan).
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In the hippocampus, neural stem cells (green) sit in a layer below their progeny, the granule neurons (red). When activated by extrinsic stimuli, they enter mitosis and generate neuron progenitor cells, which eventually mature into neurons and migrate into the layer above. The number of neural stem cells in the hippocampus decreases over time, possibly contributing to the cognitive impairment associated with aging. One hypothesis is that, after a rapid series of divisions, these neural stem cells disappear via their conversion into astrocytes.

Image: Section of a mouse hippocampus imaged with Zeiss LSM 50 confocal microscope with a 40X C-Apochromat water-immersion objective lens (N.A. value 1.2, working distance 220 microns) at 62x magnification. Brain slices were fixed in 4% paraformaldehyde, immunolabeled, and then cleared in FocusClear (CelExplorer, Taiwan).

Source: download.cell.com